BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
Lars Larsson
eRA COMMONS USER NAME: LARSLARSSON
POSITION TITLE
Professor & Chair
EDUCATION/TRAINING
INSTITUTION AND LOCATION
Karolinska Institute, Stockholm (accepted into
School of Medicine, Karolinska Institute 1971)
Department of Physiology, Karolinska Institute
Karolinska Institute, Stockholm
Karolinska Institute, Stockholm
Karolinska Institute, Stockholm
DEGREE
(if
applicable)
MM/YY
Med. Kand.
1973
Medicine
Ph.D.
M.D
Specialist
Docent
1978
1982
1985
1985
Physiology
Medicine
Clinical Neurophysiology
Physiology
FIELD OF STUDY
A. Positions
Positions and Employment
1975-1976
Temporary M.D. appointment as orthopedic surgeon, Linköing hospital,
Södersjukhuset
1973-1977
Research assistant, Department of Physiology III , Karolinska Institute, Stockholm.
1977-1978
Research assistant, Laboratory of Human Performance, National Defense Research
Institute, Stockholm.
1978 (Oct.-Dec.)
Post-Doctoral Student Biomechanical Laboratory, Penn State University,
Pennsylvania, USA.
1979-1982
Research assistant, Department of Physiology III (neurophysiology), Karolinska
Institute, Stockholm.
1980-1982
Internship, Nacka Hopsital and Södersjukhuset, Stockholm
1982-1985
Residency training in Clinical Neurophysiology at the Department of Clinical
Neurophysiology and Neurology , Karolinska Hospital, Stockholm.
1985
Granted the qualification as a specialist in Clinical Neurophysiology by the National
Swedish Board of Health and Welfare.
1985-1998
Associate Professor (docent) in physiology, Karolinska Institute, Stockholm.
1986-1998
Assistant senior physician (biträdande överläkare), Department of Clinical
Neurophysiology, Karolinska Hospital, Stockholm.
1988 (Nov. -Dec.)
Visiting scientist, Padova University, Italy.
1991-1992
Visiting scientist, Dept. of Physiology, School of Medicine, University of WisconsinMadison, WI, USA.
1997-2002
Marie Underhill Noll Professor at the Noll Physiological Research Center, The
Pennsylvania State University, USA
1997-2002
Adjunct Professor the Department of Cell and Molecular Physiology, Hershey Medical
School, Penn State University, USA
1997-2000
Director, General Clinical Research Center, University Park, The Pennsylvania State
University
1998-2002
Endowed Professor, The Pennsylvania State University
1999-present
Adjunct Professor, Department of Clinical Neuroscience, Karolinska Institute,
Stockholm, Sweden
2001-2002
Interim Director, Noll Physiological Research Center, The Pennsylvania State
University.
2002-present
Professor & Chair, Department of Clinical Neurophysiology, Uppsala University
Hospital and Uppsala University, Uppsala, Sweden
2002-2008
20082007200820092008-2010
2011-2013
Research Professor, Center for Developmental & Health Genetics, The Pennsylvania
State University
Research Professor, Department of Biobehavioral Health, The Pennsylvania State
University
Academic Chair, (Divisionsprefekt) Division of Clinical Neuroscience, Uppsala
University Hospital, Uppsala, Sweden
International Affiliate, Center for Muscle Biology, Univ of Kentucky, Lexington
Chairman, Research Committee, Department of Neuroscience, Uppsala University
Member, Musculoskeletal Study Section, Karolinska Hospital
Chairman, Musculoskeletal Study Section, Karolinska Hospital
C. Selected Peer-reviewed Publications (Selected from more than 175 peer-reviewed publications)
Most relevant to the current application
1. Larsson, L., Li, X., Edström, L., Eriksson, L.I., Zackrisson, H., Argentini, C., Schiaffino, S. 2000. Loss of
muscle myosin and acute quadriplegia in patients treated with non-depolarizing neuromuscular blocking
agents and corticosteroids. Underlying cellular and molecular mechanisms. Critical Care Medicine 28:3445.
2. Larsson, L. 2007. Experimental animal models of muscle wasting in intensive care unit patients. Critical
Care Medicine 35(9 Suppl):S484-7
3. Ochala, J., Gustafson, A.-M., Li, M., Aare, S., Qaisar, R., Llano Diez, M., Banduseela, V., Hedström, Y,
Tang, X, Dworkin, B, Nair, S, Ford, C., Perera, S., Gautel, M., Larsson. L. 2011. Preferential skeletal
muscle myosin loss in response to mechanical silecing in a novel rat intensive care unit model: underlying
mechanisms. J Physiol (Lond) 589 (8): 2007-2026.
4. Larsson, L., Ansved, T. 1995. Effects of ageing on the motor unit. Progress in Neurobiology 45, 397-458.
5. Larsson, L., Moss, R.L. 1993. Maximal velocity of shortening in relation to myosin isoform composition in
single fibres from human skeletal muscles. Journal of Physiology 472:595-614.
6. Cristea, A., Karlsson Edlund, P., Lindblad, J., Qaisar, R., Bengtsson, E., Larsson, L. 2010. Effects of
ageing and gender on the spatial organization of myonuclei in single human skeletal muscle cells. Aging
Cell 9:685-697.
7. Ochala, J., Renaud, G., Llano Diez, M., Banduseela, V., Aare, S., Ahlbeck, K., Radell, PJ, Eriksson, LI.,
Larsson, L. 2011. Diaphragm muscle weakness in an experimental intensive care unit model. PLOS one
Vol 6 Issue 6 e20876
8. Llano-Diez, Gustafson, A.-M., Olsson, C., Goransson, H., Larsson, L. 2011. Muscle wasting and the
temporal gene expression pattern in a novel rat intensive care unit model. BMC Genomics. 2011 Dec
13;12(1):602.
9. Llano-Diez, M., Renaud,G., Andersson, Gonzales, H., M., Hedström, Y., Corpeno, R., Engqvist, H.,
Bergquist, J., Larsson L. 2012. Passive mechanical loading improves muscle function but not mass in
immobilized intensive care unit patients. Critical Care 16:R209 doi:10.1186/cc11841 Highly Accessed
BMC Journal publication
10. Renaud,G., Llano-Diez, M., Gorza, L., Gustafson, A-M., Li, M., Hedström, Y., Ford, G. C. , Nair, K. S. ,
Perera, S. , Gautel, M., Jin, J.P., Larsson L. 2013. Sparing of muscle mass and function by passive
loading in an experimental intensive care unit model J Physiol. Jan 2. [Epub ahead of print]
Additional recent publications of importance to the field
1. Aare, S., Ochala, J., Göransson, H., Norman, HS, Radell, P., Eriksson, LI., Larsson, L. 2011.
Mechanisms underlying the sparing of masticatory muscle function in an experimental critical illness
model. Physiol Genomics. Dec 16;43(24):1334-50.
2. Höök, P., Vidyasagar, S., Larsson, L. 2001. Effects of aging on actin sliding speed on myosin from single
mouse, rat and human skeletal muscle cells. American Journal of Physiology:Cell 280: C782-C788.
3. Lionikas A., Blizard D.A., Vandenbergh D.J., Stout J.T., Vogler G.P., McClearn G.E., Larsson L. 2006.
Genetic determinants of weight of fast- and slow-twitch skeletal muscles in old mice. Mammalian Genome.
17:615-628.
4. Stelzer,J.E., Larsson, L. Fitzsimons, D.P., Moss, R.L. 2006. Activation dependence of stretch activation in
mouse myocardium. Implications for ventricular function. J General Physiology 127; 95-107.
5. Höök, P., Larsson, L. 2000. Actomyosin interactions in a novel single muscle fiber in vitro motility assay.
Journal of Muscle Research and Cell Motility 21:357-365.
6. Li, M., Lionikas, A., Yu, F., Tajshargi, H., Oldfors, A.. Larsson, L. 2006. Myosin function in patients with a
IIa myosin heavy chain E706K mutation. Neuromuscular Disorders 16(11):782-91
7. Nordquist, J., Höglund, A.S., Norman, H., Dworkin, B. Larsson, L. 2007. Transcription factors in muscle
atrophy caused by long-term post-synaptic block of neuromuscular transmission and muscle unloading in
rats. Molecular Medicine 13(9-10):461-70.
8. Ochala, J., Li, M., Tajsharghi, H., Kimber, E., Tulinius, M., Oldfors, A., Larsson, L. 2007 Effects of a
R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres.
Journal of Physiology 15;581(Pt 3):1283-92.
9. Ochala, J., Larsson, L. 2008. Effects of myosin heavy chain loss on the regulation of Ca2+-activation in
single human skeletal muscle fibres. Experimental Physiology 93(4):486-95.
10. Ochala, J., Iwamoto, H., Larsson, L. Yagi, N. 2010. A myopathy-linked tropomyosin
mutation severely
alters thin filament conformational changes during activation. Proc Natl Acad Sci U S A. May
25;107(21):9807-12
D. Research Support
Ongoing Research Support
K2003-32X-08651
1/1/12-12/31/15 ($216 000)
The Swedish Research Council (PI: Larsson)
Muscle wasting and loss of muscle function with specific reference to sarcomeric protein structure and
function: Underlying mechanisms, improved diagnostics and specific intervention strategies
The goal of this study is to unravel the mechanisms underlying the Acute Quadriplegic Myopathy (AQM) in limb
muscles from critically ill ICU patients, improve diagnostics and test specific interventions (primarily the effect
of passive mechanical loading)
No number. 7/1/10-6/31/13 ($ 40 000)
STINT (International collaborative grant: Sweden-Australia-Japan) (PI: Larsson)
Aging-related changes in skeletal muscle structure- function and specific intervention strategies: A translational
approach to unravel underlying mechanisms
The goal of this project is to improve our understanding of aging-related changes in skeletal muscle structure
and function by combining cell/molecular physiological, gene transfer, X-ray diffraction and mass spec
analyses. This is an international collaborative grant supporting annual meetings and exchange of students,
but it does not support ongoing research projects.
CM1001 7/1/10-6/31/13 ($ 20 000)
EU-COST project (PI: T Grune)
Chemistry of non-enzymatic protein modification - modulation of protein
structure and function
The goal of this project is to stimulate interactions among European research groups working on posttranslational protein modifications, i.e., annual meetings and exchange of students between groups. No
support for research
MyoAge 1/1/09 –12/31/12 ($ 200 000, to Larsson)
EU-Large scale integrating project (PI: Butler-Browne; Project leader: Larsson)
Understanding and combating age-related muscle weakness
Large scale EU-project including 18 different groups. The role of the applicant is to unravel aging-related posttranslational myosin modifications in human limb muscles and the effects of myosin function.
No number. 1/1/11-12/31/12 ($30,000)
King Gustaf V and Queen Victoria Foundation (P.I. L. Larsson)
Effects of aging on regulation of human muscle structure and function: Effects of physical activity and
hormone replacement therapy in post-menopausal women
The effects of 1) life-long physical activity in master athletes or 2) hormone replacement therapy (HRT) in
postmenopausal HRT discordant monozygous twin pairs on regulation of muscle contraction and myonuclear
organization at the muscle cell level. (Collabioration with University of Jyväskylä, Finland).
No number, 1/1/10-12/31/11 ($105,000)
Completed Research Support
No number, 3/1/06-2/28/08 ($30,000)
Association Francaise centers les Myopathies (AFM) (PI:Larsson)
Acute quadriplegic myopathy:underlying mechanisms at the gene, protein and muscle cell level
mRNA, protein and single cell contractile measurements in the porcine AQM model
No number, 9/1/06-8/31/07 ($21,960 )
National Center for Medical Rehabilitation Research (NCMRR) (PI:Hoffman, I:Larsson)
Acute quadriplegic myopathy:underlying mechanisms
Microarray analyses of pig samples at the Research Center for Genetic Medicine, Children's National Medical
Center, Washingto, DC. M. biceps femoris samples obtained from 22 pigs at three different occasions during a
5-day period.
No number, 1/1/06-12/31/07 ($25,000)
Swedish Cancer Society (PI:Larsson)
Cancer cachexia and loss of myofibrillar proteins: underlying mechanisms
Clinical studies on mechanisms underlying severe muscle wasting and weakness in patients with cancer.
AR47318 07/01/01-06/30/03 ($250,000)
NIAMS R01 (PI: Larsson)
Shortening velocity and scaling: Underlying mechanisms
Mechanisms underlying the altered contractile speed in muscle cells expressing different myosin isoforms in
mammalian species with a large variation in body size.
AR45627 08/01/00-07/31/03 ($250,000)
NIAMS R01 (PI: Larsson)
Sarcopenia: Underlying Mechanisms
Cellular and molecular mechanisms underlying the aging-related decrease in force and contractile speed in
humans.
AG014731 10/1/02-9/30/04 ($200,000)
NIA (competitive supplement to P01, G. McClearn PI: $1,060,469) (Supplement PI: Larsson)
QTL Analysis of Age-Related Phenotypes
QTL analysis of sarcopenia.